Is letrozole superior to clomiphene for infertility treatment among individuals with polycystic ovarian syndrome?
This meta-analysis of randomized controlled trials showed that for individuals with PCOS, treatment of infertility with letrozole as compared with clomiphene citrate, resulted in higher rate of ovulation induction, more pregnancies, and more live births. The conclusions are less than certain due to the high risk of bias in some studies.
Meta-analysis (randomized controlled trials)
Self-funded or unfunded
These authors conducted a meta-analysis of randomized controlled trials (N = 29 with 3952 participants and 7633 ovulation induction cycles) to compare the effect of letrozole and clomiphene citrate on fertility among individuals with polycystic ovarian syndrome (PCOS). They included studies that met the criteria of diagnosis of PCOS based on the Rotterdam 2003 criteria, had timed intercourse or insemination, and reported at least 1 of the 3 outcomes of interest. Seven studies were graded as having high risk of bias to one or more of the following: quasi-randomization (n = 3), lack of fully described allocation concealment (n = 3), lack of masking (n = 6), or differences between groups in duration of infertility (n = 1). Meta-analysis for all primary outcomes favored letrozole; ovulation induction rate (22 studies with 6862 participants; 67% vs 59%; relative risk [RR] 1.14; 95% CI 1.06 - 1.21; P <.001), pregnancy rate (28 studies with 3936 participants; 35% vs 23%; RR 1.48; 1.34 - 1.63, P < .001), and live birth rate (8 studies with 1725 participants; 33% vs 22%; RR 1.49; 1.27 - 1.74; P < .001). The authors judged the certainty of evidence to be low for ovulation induction rate, and moderate for both pregnancy and live birth rate.
Linda Speer, MD
Professor and Chair, Department of Family Medicine
University of Toledo